Certain phosphorus acid esters as disinfectants

ABSTRACT

A disinfectant is provided which contains as active ingredient a compound of the formula I   in which R1 and R2 each represents hydrogen or methyl, R3, R4, R5, R6 and R8 each represents hydrogen or an alklyl radical having from 1 to 4 carbon atoms, R7 represents an alykl or alkenyl radical having from 8 to 18 carbon atoms, N STANDS FOR 2 OR 3, M IS ZERO OR A NUMBER FROM 1 TO 4, IN THE CASE OF M BEING 1 TO 4, R2 represents hydrogen and, in the case of m being zero, R3 R4 must be hydrogen if R1 and R2 are methyl and R4 must be hydrogen if R3 represents propyl or butyl. The disinfectant is effective against bacteria and stages of helminths.

United States Patent [191 Diiwel et al.

[ June 10, 1975 CERTAIN PHOSPHORUS ACID ESTERS AS DISINFECTANTS PrimaryExaminer-V. D. Turner Attorney, Agent, or Firm-Curtis, Morris & Safford[57 ABSTRACT A disinfectant is provided which contains as activeingredient a compound of the formula I [73] Assignee: HoechstAktiengesellschaft,

Frankfurt am Main, Germany [22] Filed: Aug. 9, 1973 [21] App]. No.:386,858

[30] Foreign Application Priority Data Aug. I2, 1972 Germany 2239790Apr. 14, 1973 Germany 23l9046 [52] US. Cl. 424/199; 424/211; 260/924[51] Int. Cl A01n 9/36 [58] Field of Search 424/l99, 211; 260/924 [56]References Cited UNITED STATES PATENTS 3,490,743 l/l970 Schmitz et al.424/2 l l in which R and R each represents hydrogen or methyl,

R R R R and R each represents hydrogen or an alklyl radical having from1 to 4 carbon atoms, R represents an alykl or alkenyl radical havingfrom 8 to 18 carbon atoms, n stands for 2 or 3, m is zero or a numberfrom i to 4, in the case of m being 1 to 4, R represents hydrogen and,in the case of m being zero, R R must be hydrogen if R and R are methyland R must be hydrogen if R represents propyl or butyl. The disinfectantis effective against bacteria and stages of helminths.

llClaims, No Drawings CERTAIN PHOSPIIORUS ACID ESTERS AS DISINFECTANTSThe present invention relates to a disinfectant which is effectiveagainst most different bacteria, as well as against stages of helminths,especially eelworm eggs.

A great number of disinfecting substances is known which are used in themost different fields of application, for example acids and lyes,chlorine or formaldehyde separating agents, cresol, lysol, andorgano-metal compounds. The said disinfectants have various drawbacks,such as corrosive action on many materials, toxicity, allergenic action,or unpleasant odor.

The present invention provides a disinfectant characterized by a rapidand complete disinfecting action without having the aforesaiddisadvantages.

The object of the present invention is, therefore, a disinfectantcontaining as active ingredient a compound of the formula I in which R,and R each represents hydrogen or methyl,

R R R R and R each represents hydrogen or an alkyl radical having from 1to 4 carbon atoms, R represents an alkyl or alkenyl radical having from8 to 18 carbon atoms, n stands for 2 or 3, m is an integer from 0 to 4,when m being 1 to 4, R represents hydrogen and,

when m is zero, R and R must be hydrogen if R and R are methyl, and

R must be hydrogen if R represents propyl or butyl. The compounds offormula I have a high killing effect on different pathogenic germs evenin low concentration and after a short time of action. The preparationsof compounds of formula I, preferably their aqueous solutions have apronounced killing effect on worm eggs and in this respect they aresuperior to known disinfectants.

The compounds of formula I are prepared by reac'ting a cyclic phosphiteof the formula II in which the substituents R to R and m have the abovemeaning. The reaction components are expediently reacted in a proportionof about 1 mole of amine to l mole of phosphite. In some cases it mayalso be suitable to use one component, preferably the amine, in a slightexcess. The reaction is preferably performed at a temperature in therange of from 60 to 150C. Depending- EXAMPLES OF PREPARATION l. 3-(3-Coconut a1kylaminopropyl-ammonium )-2,2- dimethylpropyl-phosphorousacid ester.

15.0 g (0.1 mole) of 2-ox0-(2H)-5,5-dimethyl-l,3- dioxa-Z-phosphorinaneand 27.4 g (0.1 mole) of coconut alkyl-propylene diamine in cc of waterwere refluxed for 2 hours while stirring. The solution was evaporated todryness and 40 grams of a compound of the following formula wereobtained 3 L H- 0 CH2 CH2 (CH2)3-NH-R 2 CH3 H in which R represents analkyl radical with the chain distribution of coconut oil fatty acid.

Equivalent weight found 436 calculated 424, Nitrogen calculated 6.6%,found 6.4 7:.

2. 3-Dodecylammonium-2,2-dimethylpropylphosphorous acid ester.

30.0 g (0.2 mole) of 2-oxo-(2H)-5,5-dimethyl-1,3- dioxa-2-phosphorinaneand 44.4 g (0.2 mole) of dodecyl amine in 100 cc of water were refluxedfor 2 hours while stirring. The solution was evaporated to dryness. 73.0g of the compound of the following formula were obtained CH H H F 0 ca c3 ca it n 0 CH H Equivalent weight calculated 387, found 383 Nitrogencalculated 3.6 71, found 3571 Phosphorus calculated 8.0%, found 78%.

In analogous manner the following compounds were prepared:

3.3-[2-(2-Dodecylamino-ethyl)-aminoethylammonium]-2,2-dimethylpropyl-phosphorousacid ester of the formula H H if T 3 H O CH C CH -Iil (CH NH C H 0 CH Ha 2 Equivalent weight calculated 421, found 440 CH3 H Nitrogencalculated 10.0%. found 9.? a. l

H-- --O-CH--CI-I-NCH 4. 3-(3-Coconutalkylaminopropyl-ammonium)-prol0 2 I2 I 18 37 pyl-phosphorous acid ester of the following formula O CH H T aH Ii 0 CH CH CH 1i (CH NH B.

in which R represents the alkyl radical having the chain EquivalentWeight Calculated 406, found 386 distribution of coconut oil fatty acid.20 calculated found 9.3-Octadecenylammonium-2,Z-dimethylpropylphosphorous acid ester of theformula Equivalent weight calculated 396. found 400 Nitrogen calculated7.1 "7(, found 6.9 71.

0 CH H 5. 3-Coconut alkyl-ammonium-Z,Z-dimethylpropyl- I i phosphorousacid ester of the following formula H 0 2 T 2 7 f 18 34 E (3H H 0 CH HH- -o-ca -c-ca N-R 2 2 I Equivalent weight calculated 4l0, found 451 CHH Nitrogen calculated 3.4 7:, found 3.2 7:.

in which R represents an alkyl radical having the3'(Dimethyldodeoyl'ammonium)'ProPl/lchain distribution of coconut oilfatty acid. Phosphorous acid ester of the formula Equivalent weightcalculated 365, found 380 H Nitrogen calculated 3.87: found 3.8%. I v 3H-P-O-CH -CH -CIi,-N-C H 6. 3-Dodecylammonium-propyl-phosphorous acid 22 12 25 ester of the formula 0 CH 0 C i H- -CH-H-CH-N-CH 2 2 2 12 25Equivalent weight calculated 359, found 345 Nitrogen calculated 3.9 7!,found 3.9 7r.

E I l l I 1309 f (1331l1.3-(Dodecylmethyl-amrronium)-2,2-dimethylproig'g s I gg gfi gtg 83:pyl-phosphorous acid ester of the following formula 7.3-Octylammonium-2,Z-dimethylpropylphosphorous acid ester of the formulaI I n a 0 3 H 0 01x c cn I|\ c n H-P-O-CH -C-CH -N-C H 3 H 0 CH HEquivalent weight calculated 287, found 307 Equivalent weight calculated344, found 362 Nitrogen calculated 4.97:. found 4.7 "/1. Nitrogencalculated 4.! 71, found 3.9 7:.

8. 3-Octadecylammonium-2,2-dimethylpropyl l2. 3(Dodecyl-diethyl-ammonium)-l-methyl-prophosphorous acid ester of theformula pyl-phosphorous acid ester.

l3. 3-( Decyl-butyl-ammonium )-2,2-diethyl-propylphosphorous acid ester.

14. 3-Octadecy1-ammonium-2-butyl-propylphosphorous acid ester.

18 hours at 37C. The minimum inhibitive concentration is the minimumconcentration (unit by weight per milliliter of test solution) found inthe series dilution test, of an antibacterially active substance atwhich a 15. 3-Dodecyl-ammonium-l,l-dimethyl-propyl- 5 growth of thetested organisms could no longer be obphosphorous acid ester. served.The tests were carried out with the compounds 16. 3-(Ole l-but1-ammonium)-2-but lro 'lof Exam les 1, 3, and 4. The results of thetests are y y P P) P phosphorous ac1d ester. summanzed 1n Tables I andll. 17. 3-Decyl-ammonium-2,Z-diethyl-propyl- Table I phosphorous acidester.

3 (octaqecybethyl'ammomum) zethyl propyl Minimum inhibitiveconcentration phosphorous ac1d ester. (unit by weight/m1) l9.3-[2-(2-Octylaminoethvl )-aminoethyl- WP of germ Compound 1 comparativeproduct ammonium]-2-methyl-2-propyl-propyl-phosphorous acid ester.SUlflLptlrlllyp/ll: A 3.9 y 15.6 7 20. 3-( 3-Coconutalkylmethyl-aminopropyly 7 oranu'nburg 15.6 7 31.5ammomum)-2-butyl-2-ethyl-propyl-phosphorous acid 78 y 315 y ester. g 71546 7 Sliige/Iu flexneri 7.8 7 15.6 7 2 1. 3-[3-(3-C oconutalky1am1nopropyl)- E coll-026 15 31.5 yam1nopropy1-ammon1um]-l-methyl-propyl- 055 3.9 'y l5.6 -y phosphorousacid ester. 8;: 22 7 7 The antibacterial activity of the compounds offor- 0114 319 z [5:6 mula I was examined in a series d1lut1on test inanalogy 012/6 3% Y :g-g Y to the prescriptions of Deutsche Gesellschaftfuer l-lyl, ""f f 7 5 7 l lrOglllLS y t 'Y giene und Mikroblologle. Ascomparatlve substance a Pfll'llLO/Ob. Hafm'a 15.6 -y 31.5 y commercialamphoteric compound of the formula y Prm'idencia 3 l .5 'y 125 y Cl2H25NH+CH2)2 NH-(CH2)2 NH CH' Kelbs pneumoniae 6.25 y 7.8 'y

0 H Prol. mirabilis 625 7 1.25 mg 60/3 625 'Y Y 1 12/3 1.25 mg 1.25 7166/3 625 7 1.25 was used- 174/3 156 y 1.25 mg The substances to betested were diluted 1n geometri- P501121. aeruginoxu 15.6 31.5 7 callydescending series (factor 2) with Merck-I bouilz lon and inoculated with2 drops each of a bacteria cul- 880/2 1516 'y 6225 7 ture 24 hours oldand diluted in a ratio of l to 100. The 2467/2 -6 7 62.5 7 2520/2 15.6 762.5 y results were ascertained after an incubatlon per1od of Table 1]Minimum inhibitive concentration (unit by weight/ml) type of germcompound compound comparative 3 product Sulm.pamlyphi .4 6.25 7 12.5 73.1 y ryplu' murium 12.5 7 12.5 y 12.5 y uranium/71ml, 25 y 6.25 y 25 yI \'p/1i 12.5 7 6.25 y 12.5 -y uriun 12.5 V 6.25 7 6.25 'y gin 12.5 6.25y 25 y .S'lu'gellu flame/'1' 6.25 7 6.25 7 12.5 7 E. 0011' 026 6.25 76.25 12.5 y 055 6.25 7 6.25 'y 25 y 078 6.25 'y 12.5 'y 25 'y 086 12.5 y12.5 'y 25 'y 0114 6.25 'y 12.5 7 25 (H26 6.25 7 12.5 'y 25 'yAcrubacu'r vluucac 6.25 6.25 7 25 ucrogem'x 1 2.5 'y 25 y y Farm-01012.Hafniu 12.5 'y 12.5 y 25 y Bel/lesdu- 12.5 y 6.25 7 12.5 y BallcrupPrmizlenciu 3v 1 y 1 2.5 -y 50 y Klebx pneumoniae 3. l 6.25 7 12.5 PIUI.mirubi/ix 500 y 250 y 1 mg /3 250 -y 250 y 1 mg 1 12/3 250 'y 250 'y 1mg 166/3 250 y 250 y 1 mg 174/3 250 'y 125 'y 1 mg Rs'eud. ucrugirmxu12.5 y 6.25 y 50 7 25 12.5 7 50 y /2 12.5 12.5 7 50 'y 880/2 12.5 y 12.57 50 y 2467/2 25 12.5 50 y 2520/2 25 y 25 y 50 -y The killing effect onworm eggs of the compounds of formula I was determined according to thefollowing method:

Eggs of a female eelworm were collected and subjected to the action ofthe test substances for the periods of time and at the concentrations asindicated in the following Table III. The preparations were then washedfive times with water with decantation and the eggs were incubated for 4weeks at 37C. After terminationof embryogenesis the number of mobile(developed) embryos was ascertained in comparison to the untreatedeelworm eggs and the infectivity of the eggs treated by the testsubstances was tested on mice. To this effect each time 10,000 oftreated eggs were orally administered to mice. Days after administrationthe mice were killed and lung and liver of the dissectedmice wereexamined as to the presence of ascarides larvae.

A 100 percent disinfection effect was obtained when the embryogenesiswas reduced by 100 percent, no mobility of the embryos did exist and noascarides larvae could be found in the mouse.

In the following Table III the disinfecting activity of the compounds 1,and 3 to 1 l of formula] specified in the examples of preparation isshown in comparison to the relevant commercial product Dekaseptol.

Table III concentration killing rate applied compound time (min) 100%I007: I007: 100% [0091' 807: 80% 90% 1007: I007: 80%

Dekaseptol" For application, the disinfectant is generally diluted withwater to a content of active ingredient in the range of from 0.5 to 10percent by weight.

What is claimed is: v

1. A disinfectant composition comprising a disinfectant amount of anactive compound of the formula in which R and R each represents hydrogenor methyl,

R R R R and R each represents hydrogen or alkyl of from 1 to 4 carbonatoms, R represents alkyl or alkenyl of from 8 to 18 carbon atoms,

it stands for 2 or 3,

m is an integer from zero to 4,

R being hydrogen when m is 1 to 4,

R and R being hydrogen when m is zero and R, and

R are methyl, and

R being hydrogenwhen m is zero and R is propyl or butyl, said activecompound being present in an amount of from 20 to 90 percent by weight,the balance being water. I

2. The disinfectant composition as defined in claim 1, wherein theactive compound is present in an amount of from 40 to percent by weight.

3. The disinfectant composition as claimed in claim 1, wherein theactive ingredient is 3-(3- coconutalkylaminopropyl-ammonium)-2,2-dimethylpropyl-phosphorous acid ester.

4. The disinfectant composition as claimed in claim 1, wherein theactive ingredient is 3-[2-(2-dodecylaminoethyl)-aminoethyl-ammonium]-2,2- dimethylrpropyl-phosphorousacid ester.

5. The disinfectant composition as claimed in claim '1, wherein theactive ingredient is 3-(3- coconutalkylaminopropyl-ammoniumpropylphosphorous acid ester.

6. The disinfectant composition as claimed in claim wherein the activeingredient is 3-dodecylammonium-2,2 dimethylpropyl-phosphorous acidester.

7. The disinfectant composition as claimed in claim 1, wherein theactive ingredient is3-coconutalkylammonium-Z,2-dimethylpropylphosphorous acid ester.

8. The disinfectant composition as claimed in claim 1, wherein theactive ingredient is 3-octadecenylammonium-2,2-dimethylpropylphosphorousacid ester.

9. The disinfectant composition as claimed in claim 1, wherein theactive ingredient is 3-(dimethyldodecyl-ammonium)-propyl-phosphorousacid ester.

10. A method of disinfecting a room, yard or animal run which comprisesapplying a disinfectant amount of the active compound defined in claim 1to the room, yard or animal run to be disinfected.

11. The method defined in claim 10 wherein the active compound isdiluted with water to a concentration of 0.5 to 10 percent by weight.

1. A DISINFECTANT COMPOSITION COMPRISING A DISINFECTANT AMOUNT OF ANACTIVE COMPOUND OF THE FORMULA
 2. The disinfectant composition asdefined in claim 1, wherein the active compound is present in an amountof from 40 to 70 percent by weight.
 3. The disinfectant composition asclaimed in claim 1, wherein the active ingredient is3-(3-coconutalkylaminopropyl-ammonium)-2,2-dimethylpropyl-phosphorousacid ester.
 4. The disinfectant composition as claimed in claim 1,wherein the active ingredient is3-(2-(2-dodecylaminoethyl)-aminoethyl-ammonium)-2,2-dimethyl-propyl-phosphorous acid ester.
 5. The disinfectant composition as claimed inclaim 1, wherein the active ingredient is3-(3-coconutalkylaminopropyl-ammonium)-propylphosphorous acid ester. 6.The disinfectant composition as claimed in claim 1, wherein the activeingredient is 3-dodecyl-ammonium-2,2-dimethylpropyl-phosphorous acidester.
 7. The disinfectant composition as claimed in claim 1, whereinthe active ingredient is3-coconutalkyl-ammonium-2,2-dimethylpropylphosphorous acid ester.
 8. Thedisinfectant composition as claimed in claim 1, wherein the activeingredient is 3-octadecenyl-ammonium-2,2-dimethylpropylphosphorous acidester.
 9. The disinfectant composition as claimed in claim 1, whereinthe active ingredient is3-(dimethyl-dodecyl-ammonium)-propyl-phosphorous acid ester.
 10. Amethod of disinfecting a room, yard or animal run which comprisesapplying a disinfectant amount of the active compound defined in claim 1to the room, yard or animal run to be disinfected.
 11. The methoddefined in claim 10 wherein the active compound is diluted with water toa concentration of 0.5 to 10 percent by weight.